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Megabase DNA Sequencing System

Project Team

Ming Xiao, PhD School of Biomedical Engineering, Science and Health Systems

Dharma Varapula School of Biomedical Engineering, Science and Health Systems

Lahari Uppuluri Mechanical Engineering Department

Moses Noh, PhD Mechanical Engineering Department


DNA sequencing (global market projected $24.5B (2023) is a technically challenging process and has become vital to interpreting human health. Short-read sequencing (SRS, Illumina sequencing), although less expensive and very accurate, still cannot detect significant numbers of genetic mutations. Long-read sequencing (LRS) is increasingly being used for this but current technologies fall short in terms of read-length, throughput, and accuracy. Often, SRS and LRS are combined to detect disease-associated structural variants (SVs), making the process complex, resource-intensive, and expensive, but still miss clinically relevant large mutations. Here, we developed a DNA sequencing system – a microdevice for DNA manipulation, sequencing kit reagents, imaging system, and data analysis software – that is capable of sequencing base-by-base from fixed megabase-long single DNA molecules. This way, sequencing of complex and repetitive regions can be efficiently performed, and a single platform may be used to detect a wide range of genetic variants at low cost and high throughput. The first milestone is to achieve optical mapping of megabase-long DNA combined with sequencing up to 10 bp, which will make the technology suitable for development of clinically relevant assays. This will also demonstrate the potential of full capability of the Megabase Sequencing System. We aim to target the research markets before expanding into clinical applications, a strategy similar to that of other platform LRS technologies.